Dataset Information

Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

ABSTRACT: Background. ?Interferon-free direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) provide a major advance in clinical management, including in human immunodeficiency virus (HIV)/HCV coinfection. Drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) require consideration. This study aimed to characterize the cART regimens in HIV/HCV-coinfected individuals and assess the clinical significance of DDIs with DAAs in a real-world cohort. Methods. ?This analysis included participants enrolled in CEASE-D, a prospective cohort of HIV/HCV-coinfected individuals in Sydney, Australia, between July 2014 and December 2015. A simulation of potential DDIs between participants' cART and interferon-free DAA regimens was performed using www.hep-druginteractions.org and relevant prescribing information. Results. ?In individuals on cART with HCV genotype (GT) 1 and 4 (n = 128), category 3 DDIs (contraindicated or not recommended) were noted in 0% with sofosbuvir/ledipasvir, 0% with sofosbuvir plus daclatasvir, 17% with sofosbuvir/velpatasvir, 36% with ombitasvir/paritaprevir/ritonavir ± dasabuvir, 51% with grazoprevir/elbasvir, and 51% with sofosbuvir plus simeprevir; current cART regimens were suitable for coadministration in 100%, 100%, 73%, 64%, 49%, and 49%, respectively. In individuals with HCV GT 2 or 3 (n = 53), category 3 DDIs were evident in 0% with sofosbuvir plus daclatasvir, 0% with sofosbuvir and ribavirin, and 13% with sofosbuvir/velpatasvir; current cART regimens were suitable in 100%, 100%, and 81%, respectively. Conclusions. ?Potential DDIs are expected and will impact on DAA prescribing in HIV/HCV coinfection. Sofosbuvir in combination with an NS5A inhibitor or ribavirin appeared to be the most suitable regimens in this cohort. Evaluation of potential DDIs is required to prevent adverse events or treatment failure.

SUBMITTER: Martinello M

PROVIDER: S-EPMC4943543 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Martinello Marianne M Dore Gregory J GJ Skurowski Jasmine J Bopage Rohan I RI Finlayson Robert R Baker David D Bloch Mark M Matthews Gail V GV

Open forum infectious diseases 20160401 2

Background. Interferon-free direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) provide a major advance in clinical management, including in human immunodeficiency virus (HIV)/HCV coinfection. Drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) require consideration. This study aimed to characterize the cART regimens in HIV/HCV-coinfected individuals and assess the clinical significance of DDIs with DAAs in a real-world cohort. Methods. This analysis inc ...[more]

PMID: 27419177

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Project description:We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients treated with interferon-free direct-acting antiviral agent-based therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention-to-treat analysis was 92.0% (95% confidence interval, 90.9%-93.1%) overall, 93.8% (92.4%-95.0%) for no cirrhosis, 91.0% (88.8%-92.9%) for compensated cirrhosis, and 80.8% (73.7%-86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14-2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12-2.41), a baseline cluster of differentiation 4-positive (CD4+) T-cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35-3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14-2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96-1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76-4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir.ConclusionIn this large real-world study, direct-acting antiviral agent-based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus-related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct-acting antiviral agent-based regimens. (Hepatology 2018;68:32-47).

Project description:Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have higher levels of immune activation, impaired antigen-specific responses, and accelerated fibrogenesis compared to patients monoinfected with HCV. Whether different direct-acting antiviral (DAA) combinations have differential effects on immunophenotypes and functions following successful HCV therapy remain unknown. Therefore, we aimed to assess the peripheral T-cell immunophenotypes and functions in patients coinfected with HIV/HCV who were successfully treated with combination DAA treatment regimens. We analyzed peripheral blood mononuclear cells (PBMCs) at baseline and at the time of sustained viral response (SVR) from subjects treated with three different combination DAA regimens: daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks (CONQUER 2-DAA), DCV/ASV/beclabuvir (BCV) for 12 weeks (CONQUER 3-DAA), and sofosbuvir (SOF) and ledipasvir (LDV) for 12 weeks (ERADICATE study). We used flow cytometry to assess T-cell phenotypes (activation and exhaustion) and HCV-specific T-cell functions (cytokine secretion and cytotoxicity). Statistical analyses were conducted using the Wilcoxon matched-pairs signed-rank test with P < 0.05 considered significant. Overall, there was an improvement in T-cell exhaustion markers, a decrease in T-cell activation, an increase in the effector memory population, and improved T-cell function after achieving SVR, with the largest effects noted with CONQUER 3-DAA treatment. Conclusion: Treatment with DCV/ASV/BCV in patients coinfected with HIV/HCV resulted in greater restoration of the T-cell impairments and perturbations associated with HIV/HCV coinfection to an extent that was greater than that observed in either two-drug regimens. We showed that different DAA-based therapies have different immunologic outcomes after successful HCV treatment in patients coinfected with HIV/HCV. This information will be beneficial for providers when selecting the regimens for patients coinfected with HIV/HCV.

Dataset Information

Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Publications

Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Similar Datasets

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